Deferasirox, deferiprone and desferrioxamine treatment in thalassemia major patients: cardiac iron and function comparison determined by quantitative magnetic resonance imaging

Abstract

Background: Oral deferiprone was suggested to be more effective than subcutaneous desferrioxamine for removing heart iron. Oral once-daily chelator deferasirox has recently been made commercially available but its long-term efficacy on cardiac iron and function has not yet been established. Our study aimed to compare the effectiveness of deferasirox, deferiprone and desferrioxamine on myocardial and liver iron concentrations and bi-ventricular function in thalassemia major patients by means of quantitative magnetic resonance imaging.

Design and methods: From the first 550 thalassemia subjects enrolled in the Myocardial Iron Overload in Thalassemia network, we retrospectively selected thalassemia major patients who had been receiving one chelator alone for longer than one year. We identified three groups of patients: 24 treated with deferasirox, 42 treated with deferiprone and 89 treated with desferrioxamine. Myocardial iron concentrations were measured by T2* multislice multiecho technique. Biventricular function parameters were quantitatively evaluated by cine images. Liver iron concentrations were measured by T2* multiecho technique.

Results: The global heart T2* value was significantly higher in the deferiprone (34 ± 11 ms) than in the deferasirox (21 ± 12 ms) and the desferrioxamine groups (27 ± 11 ms) (P = 0.0001). We found higher left ventricular ejection fractions in the deferiprone and the desferrioxamine versus the deferasirox group (P = 0.010). Liver iron concentration, measured as T2* signal, was significantly lower in the desferrioxamine versus the deferiprone and the deferasirox group (P = 0.004).

Conclusions: The cohort of patients treated with oral deferiprone showed less myocardial iron burden and better global systolic ventricular function compared to the patients treated with oral deferasirox or subcutaneous desferrioxamine.

Figure 1.

Global heart T2* and the T2* in the mid-ventricular septum in the groups treated with deferiprone, desferrioxamine and deferasirox. There were significant differences among groups (P=0.0001). Post hoc analysis showed significantly higher global heart T2* and T2* in the mid-ventricular septum in the group treated with deferiprone versus the group treated with desferrioxamine and deferasirox. Each box shows the median, quartiles, and extreme values within the category.

Figure 2.

Left ventricular ejection fraction in the groups treated with deferiprone, desferrioxamine and deferasirox. There were significant differences among groups (P=0.010). Post hoc analysis showed a significantly higher left ventricular ejection fraction in the group treated with deferiprone versus the group treated with deferasirox. Each box shows the median, quartiles, and extreme values within the category.

Figure 3.

Estimated MRI LIC (mg/g dw) in the groups treated with deferiprone, desferrioxamine and deferasirox. There were significant differences among groups (P=0.004). Post hoc analysis showed a significantly lower LIC in the group treated with desferrioxamine versus the group treated with deferiprone and the group treated with deferasirox. Each box shows the median, quartiles, and extreme values within the category.

Figure 4.

Mean serum ferritin in the groups treated with deferiprone, desferrioxamine and deferasirox. There were significant differences among groups (P=0.002). Post hoc analysis showed a significantly higher mean ferritin value in the group treated with deferasirox versus the group treated with desferrioxamine. Each box shows the median, quartiles, and extreme values within the category.